Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl‐β‐cyclodextrin oral solution or coated‐pellet capsules
1999; Wiley; Volume: 42; Issue: 11-12 Linguagem: Inglês
10.1046/j.1439-0507.1999.00518.x
ISSN1439-0507
AutoresAxel Glasmacher, Christian Hahn, Ernst Molitor, G. Marklein, Tilman Sauerbruch, Ingo Schmidt‐Wolf,
Tópico(s)Fungal Infections and Studies
ResumoWe have previously shown that a trough concentration of at least 500 ng ml −1 itraconazole is necessary for an effective antifungal prophylaxis in neutropenic patients. Since the bioavailability of itraconazole is reduced in these patients, a satisfactory dosing regimen remains to be defined. In this study, six dosing regimens with itraconazole capsules 400, 600 or 800 mg day −1 , itraconazole solution 400 mg day −1 (additional loading dose: 400 mg day −1 solution for 2 days), 800 mg day −1 or 400 mg day −1 (additional loading dose: 800 mg day −1 capsules for 7 days, s/c1200) were compared during 160 courses of myelosuppressive chemotherapy in 123 patients with acute leukaemia. After the first week, patients taking 800 mg day −1 or 400 mg day −1 (s/c1200) itraconazole solution achieved significantly higher trough concentrations (high‐performance liquid chromatography) than patients in other groups ( P <0.05) and 87 and 100%, respectively, of these had concentrations >500 ng ml −1 . Contrary to a dose of 400 mg day −1 , a dose of 800 mg day −1 itraconazole solution induced severe nausea and vomiting in 46% of the patients. We conclude that 400 mg day −1 itraconazole solution with a loading dose of 800 mg day −1 capsules for 7 days resulted in sufficient trough concentrations from the first week onwards and appears to be suitable for antifungal prophylaxis in neutropenic patients.
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